Search

Fat mass is linked mechanistically to the cardiovascular system through leptin, a 16 kDa protein produced primarily by adipocytes. In addition to increasing blood pressure via hypothalamic-sympathetic pathways, leptin stimulates monocyte migration, cytokine secretion, and other functions that contribute to atherosclerotic plaque development. These functions are also characteristics of CD16-positive monocytes that have been implicated in the clinical progression of atherosclerosis. This investigation sought to determine if leptin promoted the development of such CD16-positive monocytes. Cells from 45 healthy men and women with age ranging from 20 to 59 years were analyzed. Circulating numbers of CD14++16++ monocytes, which are primary producers of TNFα, were positively related to plasma leptin concentrations ( P < 0.0001), with a stronger correlation in men ( P < 0.05 for leptin × sex interaction). In vitro, recombinant human leptin induced CD16 expression in a dose-related manner ( P = 0.02), with a stronger influence on monocytes from men ( P = 0.03 for leptin × sex interaction). There were no sex-related differences in total leptin receptor expression on any monocyte subtypes, relative expression of long versus short isoforms of the receptor, or soluble leptin receptor concentrations in the plasma. The number of circulating CD14+16++ monocytes, which preferentially migrate into nascent plaques, was positively related to systolic blood pressure ( R = 0.56, P = 0.0008) and intima-media thickness ( R = 0.37, P = 0.03), and negatively related to carotid compliance ( R = −0.39, P = 0.02). These observations indicate that leptin promotes the development of CD16-positive monocyte populations in a sex-specific manner and that these subpopulations are associated with diminished vascular function. [ABSTRACT FROM AUTHOR]

Background: We previously reported that a median of 5.6 years of intensive as compared with standard glucose lowering in 1791 military veterans with type 2 diabetes resulted in a risk of major cardiovascular events that was significantly lower (by 17%) after a total of 10 years of combined intervention and observational follow-up. We now report the full 15-year follow-up., Methods: We observationally followed enrolled participants (complete cohort) after the conclusion of the original clinical trial by using central databases to identify cardiovascular events, hospitalizations, and deaths. Participants were asked whether they would be willing to provide additional data by means of surveys and chart reviews (survey cohort). The prespecified primary outcome was a composite of major cardiovascular events, including nonfatal myocardial infarction, nonfatal stroke, new or worsening congestive heart failure, amputation for ischemic gangrene, and death from cardiovascular causes. Death from any cause was a prespecified secondary outcome., Results: There were 1655 participants in the complete cohort and 1391 in the survey cohort. During the trial (which originally enrolled 1791 participants), the separation of the glycated hemoglobin curves between the intensive-therapy group (892 participants) and the standard-therapy group (899 participants) averaged 1.5 percentage points, and this difference declined to 0.2 to 0.3 percentage points by 3 years after the trial ended. Over a period of 15 years of follow-up (active treatment plus post-trial observation), the risks of major cardiovascular events or death were not lower in the intensive-therapy group than in the standard-therapy group (hazard ratio for primary outcome, 0.91; 95% confidence interval [CI], 0.78 to 1.06; P = 0.23; hazard ratio for death, 1.02; 95% CI, 0.88 to 1.18). The risk of major cardiovascular disease outcomes was reduced, however, during an extended interval of separation of the glycated hemoglobin curves (hazard ratio, 0.83; 95% CI, 0.70 to 0.99), but this benefit did not continue after equalization of the glycated hemoglobin levels (hazard ratio, 1.26; 95% CI, 0.90 to 1.75)., Conclusions: Participants with type 2 diabetes who had been randomly assigned to intensive glucose control for 5.6 years had a lower risk of cardiovascular events than those who received standard therapy only during the prolonged period in which the glycated hemoglobin curves were separated. There was no evidence of a legacy effect or a mortality benefit with intensive glucose control. (Funded by the VA Cooperative Studies Program; VADT ClinicalTrials.gov number, NCT00032487.)., (Copyright © 2019 Massachusetts Medical Society.)

Holstein steer calves (n = 32; 156 ± 33.2 kg average BW) were used to evaluate the duration of restraint and isolation stress (RIS) on endocrine and blood metabolite status and the incidence of dark-cutting LM. Calves were blocked by BW and assigned randomly within blocks to one of four stressor treatments: unstressed controls (NS) or a single bout of RIS for 2, 4, or 6 h. Venous blood was collected via indwelling jugular catheters at 40, 20, and 0 min before stressor application and at 20-min intervals during RIS. Unstressed calves remained in their home stanchions and, except for blood sampling, were subjected to minimal handling and stress. Serum cortisol and plasma lactate concentrations were increased (P < 0.01) during the first 20 min after RIS application, and remained elevated throughout the 6 h of RIS. Plasma concentrations of glucose and insulin were greater (P < 0.05) in RIS calves than in NS calves after 80 and 100 min of stressor application, respectively; however, RIS did not (P > 0.80) affect plasma NEFA concentrations. Calves were slaughtered within 20 min of completion of RIS, and muscle samples were excised from right-side LM at 0, 0.75, 1.5, 3, 6, 12, 24, and 48 h after exsanguination for quantifying LM pH, and glycogen and lactate concentrations. The pH of the LM from calves subjected to 6 h of RIS exceeded 6.0, and was greater (P < 0.05) at 24 and 48 h postmortem than the pH of NS calves or calves subjected to 2 or 4 h RIS. Muscle glycogen concentrations did not differ (P = 0.16; 25.58, 10.41, 13.80, and 14.41 µmol/g of wet tissue weight for NS and 2-, 4-, and 6-h RIS, respectively), and LM lactate concentrations tended to be lower (P = 0.08) in calves subjected to 6 h of RIS. At 48 h after exsanguination, the LM from calves subjected to 6 h of RIS had more (P < 0.05) bound and less (P < 0.05) free moisture than did the LM from NS calves or calves subjected to 2 or 4 h of RIS. Additionally, the LM from RIS calves was darker (lower L* values; P < 0.05) than the LM of NS calves. Visual color scores for the LM were greatest (P <0.05) for calves subjected to 6 h of RIS and least (P < 0.05) for NS calves. Subjecting lightweight Holstein calves to 6, 4, and 2 h of RIS resulted in six (75%), two (25%), and two (25%) carcasses characteristic of the dark-cutting condition, respectively. There were no dark-cutting carcasses produced from NS calves. Thus, RIS may be a reliable animal model with which to study the formation of the dark-cutting condition. [ABSTRACT FROM AUTHOR]

Exposure to cold increases abundance of mRNA for uncoupling protein-3 (UCP3) in skeletal muscle, whereas the influence of exposure to heat is unknown. Thus, we conducted a study to investigate the influence of heat exposure on UCP3 mRNA abundance in porcine skeletal muscle. Three pigs aged 110 to 120 d, with an average BW of 75 kg, from each of eight litters were used. Each littermate was assigned to one of three treatment groups; one group was reared at 32°C and fed ad libitum (32AL) for 4 wk, whereas the other two groups were maintained at 23°C for the same period, and either pair-fed the intake of their 32AL littermates (23PF), or fed ad libitum (23AL). The RNase protection assay revealed that UCP3 mRNA abundance in longissimus dorsi and rhomboideus muscles was higher (P < 0.05) in the 32AL group than the 23PF group. The 23AL group also had significantly higher UCP3 mRNA abundance than the 23PF group in these muscles. Plasma total 3,5,3'-triiodothyronine concentration of the 32AL group was lower (P < 0.05) than that of the 23PF group, whereas mRNA abundance of thyroid hormone receptor (TR) isoforms, TRα1 and TRα2, in these muscles was not affected, suggesting that the 32AL group was in a relatively hypothyroid state. Because thyroid hormone up-regulates UCP3 expression, these results indicate that factors other than thyroid hormone may play a role in regulating UCP3 mRNA abundance in skeletal muscle of heat-exposed pigs. [ABSTRACT FROM AUTHOR]

Inquiries into poverty in the countries of the South have become a preoccupation and a focus for action among many institutions located in the North. This article interprets inquiries as cultural devices through which the complexities of North/South interactions can be analyzed. It builds on postcolonial critiques of these interactions, examining the role of inquiries in light of current debates about ethnocentrism. It examines the extent to which, in particular times and places, inquiries may act as “postcolonial” devices. The article focuses on an inquiry into poverty and development in southern Africa, known as the Second Carnegie Inquiry, which was carried out in South Africa during the 1980s with funding from the Carnegie Corporation of New York. The hybrid framework adopted combines insights from the postcolonial turn with recent work in the geographies of science. By shifting the analysis from institutions, such as the Northern philanthropic trusts, to particular devices and their contexts, the article argues that the spatial genealogies of knowledge can be traced, together with the diverse modes and relations of power on which inquiries such as those of Carnegie are based and that they also serve to produce. This approach questions the assumption that, in their exercise of power at a distance, cultural institutions have fixed or singular identities. It provides the opportunity to highlight the uncertainties that frequently lie behind a projected global image and the ways in which this image may be deliberately harnessed and manipulated for specific purposes within the South. [ABSTRACT FROM AUTHOR]

This paper examines two inquiries into poverty in South Africa funded by the Carnegie Corporation of New York, the first in the late 1920s to early 1930s and the second during the 1980s. When analysed together the inquiries offer insights into the dynamic relations and tensions between this American foundation, normative science and interpretations of poverty in South Africa during the twentieth century. The paper highlights the common ground as well as the profound differences between the inquiries and the national and international, political and institutional contexts within which they were conducted. It suggests that far from being deployed with confidence and certainty, underpinning both inquiries were contextual, institutional and intellectual uncertainties which were associated with particular visions of South Africa and the United States held by the Corporation and their funding recipients. Reference is made to the strategies employed to overcome these anxieties including the shifting notions of co-operative science they sought to promote, the contrasting meanings attached to the cultural technologies employed and the complex associations which they endeavoured to encourage. In offering a more nuanced interpretation of North–South relations than many contemporary analyses, the paper examines, through these strategies, the attempts made to satisfy the objectives of both the Corporation and its funding recipients in South Africa and the tensions which emerged over the locations of knowledge and institutional control. [ABSTRACT FROM AUTHOR]

Presents a study which evaluated abdominal adipose tissue leptin production during short-term fasting in lean and obese women. Information on leptin; Methodology of the study; Results and discussion.

Discusses a study which examined the lack of skeletal muscle uncoupling protein 2 and 3 mRNA induction during fasting in type-2 diabetic patients. Information on uncoupling proteins 2 and 3; Materials and methods; Results; Discussion.

Offers a look at a study which assessed the role of estradiol on leptin levels. Investigation on leptin's ability to reduce body weight and fat mass in lean or obese ovariectomized mice; Effects of simultaneous administration or pretreatment with estradiol on leptin's ability to reduce fat mass; Materials and methods of the study.

Deals with a study which determined the effect of sepsis on serum leptin concentration in humans. Relationship between leptin and the metabolic consequences of sepsis; Glucose infusion rates and hormone concentrations in septic patients and healthy controls; Correlation of serum leptin concentration with body fats.

Presents information on a study regarding the role of plasma tumor necrosis factor-alpha on advancing age and insulin resistance. Subjects and study design; Clinical characteristics of the subjects; Calculation and statistical analysis; Experimental results.

Aims: Cognitive decline disproportionately affects older adult type 2 diabetes. We tested whether randomized intensive (INT) glucose-lowering reduces the rate(s) of cognitive decline in adults with advanced type 2 diabetes (mean: age, 60 years; diabetes duration, 11 years) from the Veterans Affairs Diabetes Trial., Methods: A battery of neuropsychological tests [digit span, digit symbol substitution (DSym), and Trails-making Test-Part B (TMT-B)] was administered at baseline in ~1700 participants and repeated at year 5. Thirty-seven risk factors were evaluated as predictors of cognitive decline in multivariable regression analyses., Results: The mean age-adjusted DSym or TMT-B declined significantly in all study participants (P < 0.001). Randomized INT glucose-lowering did not significantly alter the rate of cognitive decline. The final model of risk factors associated with 5-year decline in age-adjusted TMT-B included as significant predictors: longer baseline diabetes duration (beta = -0.028; P = 0.0057), lower baseline diastolic blood pressure (BP; beta = 0.028; P = 0.002), and baseline calcium channel blocker medication use (beta = -0.639; P < 0.001). Higher baseline pulse pressure was significantly associated with decline in age-adjusted TMT-B suggesting a role for both higher systolic and lower diastolic BPs. Baseline thiazide diuretic use (beta = -0.549; P = 0.015) was an additional significant predictor of 5-year decline in age-adjusted digit symbol score. Post-baseline systolic BP-lowering was significantly associated (P < 0.001) with decline in TMT-B performance. There was a significant inverse association between post-baseline plasma triglyceride-lowering (P = 0.045) and decline in digit symbol substitution task performance., Conclusion: A 5-year period of randomized INT glucose-lowering did not significantly reduce the rate of cognitive decline in older-aged adults with type 2 diabetes. Systolic and diastolic BPs as well as plasma triglycerides appeared as modifiable risk factors of the rate of cognitive decline in older adult type 2 diabetes.

Aims: To evaluate the relationship between patterns of rosiglitazone use and cardiovascular (CV) outcomes in the Veterans Affairs Diabetes Trial (VADT)., Methods: Time-dependent survival analyses, case-control and 1 : 1 propensity matching approaches were used to examine the relationship between patterns of rosiglitazone use and CV outcomes in the VADT, a randomized controlled study that assessed the effect of intensive glycaemic control on CV outcomes in 1791 patients with type 2 diabetes (T2D) whose mean age was 60.4 ± 9 years. Participants were recruited between 1 December 2000 and 31 May 2003, and were followed for 5-7.5 years (median 5.6) with a final visit by 31 May 2008. Rosiglitazone (4 mg and 8 mg daily) was initiated per protocol in both the intensive-therapy and standard-therapy groups. Main outcomes included a composite CV outcome, CV death and myocardial infarction (MI)., Results: Both daily doses of rosiglitazone were associated with lower risk for the primary composite CV outcome [4 mg: hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.49-0.81 and 8 mg: HR 0.60, 95% CI 0.49-0.75] after adjusting for demographic and clinical covariates. A reduction in CV death was also observed (HR 0.25, p < 0.001, for both 4 and 8 mg/day rosiglitazone); however, the effect on MI was less evident for 8 mg/day and not significant for 4 mg/day., Conclusions: In older patients with T2D the use of rosiglitazone was associated with decreased risk of the primary CV composite outcome and CV death. Rosiglitazone use did not lead to a higher risk of MI., (© 2015 This article is a U.S. Government work and is in the public domain in the USA.)

Background: The Veterans Affairs Diabetes Trial previously showed that intensive glucose lowering, as compared with standard therapy, did not significantly reduce the rate of major cardiovascular events among 1791 military veterans (median follow-up, 5.6 years). We report the extended follow-up of the study participants., Methods: After the conclusion of the clinical trial, we followed participants, using central databases to identify procedures, hospitalizations, and deaths (complete cohort, with follow-up data for 92.4% of participants). Most participants agreed to additional data collection by means of annual surveys and periodic chart reviews (survey cohort, with 77.7% follow-up). The primary outcome was the time to the first major cardiovascular event (heart attack, stroke, new or worsening congestive heart failure, amputation for ischemic gangrene, or cardiovascular-related death). Secondary outcomes were cardiovascular mortality and all-cause mortality., Results: The difference in glycated hemoglobin levels between the intensive-therapy group and the standard-therapy group averaged 1.5 percentage points during the trial (median level, 6.9% vs. 8.4%) and declined to 0.2 to 0.3 percentage points by 3 years after the trial ended. Over a median follow-up of 9.8 years, the intensive-therapy group had a significantly lower risk of the primary outcome than did the standard-therapy group (hazard ratio, 0.83; 95% confidence interval [CI], 0.70 to 0.99; P=0.04), with an absolute reduction in risk of 8.6 major cardiovascular events per 1000 person-years, but did not have reduced cardiovascular mortality (hazard ratio, 0.88; 95% CI, 0.64 to 1.20; P=0.42). No reduction in total mortality was evident (hazard ratio in the intensive-therapy group, 1.05; 95% CI, 0.89 to 1.25; P=0.54; median follow-up, 11.8 years)., Conclusions: After nearly 10 years of follow-up, patients with type 2 diabetes who had been randomly assigned to intensive glucose control for 5.6 years had 8.6 fewer major cardiovascular events per 1000 person-years than those assigned to standard therapy, but no improvement was seen in the rate of overall survival. (Funded by the VA Cooperative Studies Program and others; VADT ClinicalTrials.gov number, NCT00032487.).

Background: The goal of the VA Diabetes Trial (VADT) was to determine the effect of intensive glucose control on macrovascular events in subjects with difficult-to-control diabetes. No significant benefit was found. This report examines predictors of the effect of intensive therapy on the primary outcome in this population., Methods: This trial included 1791 subjects. Baseline cardiovascular risk factors were collected by interview and the VA record. The analyses were done by intention to treat., Findings: Univariate analysis at baseline of predictors of a primary cardiovascular (CV) event included a prior CV event, age, insulin use at baseline, and duration of diagnosed diabetes (all P < .0001). Multivariable modeling revealed a U-shaped relationship between duration of diabetes and treatment. Modeled estimates for the hazard ratios (HRs) for treatment show that subjects with a short duration (3 years or less) of diagnosed diabetes have a nonsignificant increase in risk (HR > 1.0) after which the HR is below 1.0. From 7 to 15 years' duration at entry, subjects have HRs favoring intensive treatment. Thereafter the HR approaches 1.0 and over-21-years' duration approaches 2.0. Duration over 21 years resulted in a HR of 1.977 (CI 1.77-3.320, P < .01). Baseline c-peptide levels progressively declined up to 15 years and were stable subsequently., Interpretation: In difficult-to-control older subjects with type 2 DM, duration of diabetes altered the response to intensive glucose control. Intensive therapy may reduce CV events in subjects with a duration of 15 years or less and may increase risks in those with longer duration., (Published by Elsevier Inc.)

Background: The effects of intensive glucose control on cardiovascular events in patients with long-standing type 2 diabetes mellitus remain uncertain., Methods: We randomly assigned 1791 military veterans (mean age, 60.4 years) who had a suboptimal response to therapy for type 2 diabetes to receive either intensive or standard glucose control. Other cardiovascular risk factors were treated uniformly. The mean number of years since the diagnosis of diabetes was 11.5, and 40% of the patients had already had a cardiovascular event. The goal in the intensive-therapy group was an absolute reduction of 1.5 percentage points in the glycated hemoglobin level, as compared with the standard-therapy group. The primary outcome was the time from randomization to the first occurrence of a major cardiovascular event, a composite of myocardial infarction, stroke, death from cardiovascular causes, congestive heart failure, surgery for vascular disease, inoperable coronary disease, and amputation for ischemic gangrene., Results: The median follow-up was 5.6 years. Median glycated hemoglobin levels were 8.4% in the standard-therapy group and 6.9% in the intensive-therapy group. The primary outcome occurred in 264 patients in the standard-therapy group and 235 patients in the intensive-therapy group (hazard ratio in the intensive-therapy group, 0.88; 95% confidence interval [CI], 0.74 to 1.05; P=0.14). There was no significant difference between the two groups in any component of the primary outcome or in the rate of death from any cause (hazard ratio, 1.07; 95% CI, 0.81 to 1.42; P=0.62). No differences between the two groups were observed for microvascular complications. The rates of adverse events, predominantly hypoglycemia, were 17.6% in the standard-therapy group and 24.1% in the intensive-therapy group., Conclusions: Intensive glucose control in patients with poorly controlled type 2 diabetes had no significant effect on the rates of major cardiovascular events, death, or microvascular complications with the exception of progression of albuminuria (P = 0.01) [added]. (ClinicalTrials.gov number, NCT00032487.), (2009 Massachusetts Medical Society)